Colorectal cancer (CRC) is a common tumor that is characterized by its high mortality rate. However, the underlying molecular mechanisms that drive CRC tumorigenesis are still not clear. Clock genes have been recognized as playing key roles in tumor development. In our present study, we found the expression of TIM (encoding protein of Timeless), one of the clock genes was up-regulated in CRC tissues comparing to the corresponding normal tissues by the results of IHC and its expression was closely associated with tumor clinical stage and poor overall survival of CRC patients through analysis of clinical CRC patients. Functional studies demonstrated that TIM promoted CRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistic investigations showed that TIM plays a key role in EMT. Immunoprecipitation followed by mass spectrometry revealed that Timeless bound with Myosin-9. Furthermore, we also found TIM regulated the expression level of Myosin-9. And Myosin-9 knockdown retarded the migration and invasion of TIM-overexpressed CRC cells. Furthermore, we found the expression of TIM was regulated by histone acetylation at its promoter area. Our results show that TIM could regulate tumorigenesis of CRC by binding and regulating Myosin-9. Our results also implicate TIM as a potential prognostic biomarker and therapeutic target for CRC.

Citation Format: Xiaoqin Yuan, Yi Wang, Lei Wu. A clock gene of TIM promotes colorectal cancer tumorigenesis through binding with myosin-9 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5924.